Diane R. Woods

Mutations in the conserved domain of SRY are uncommon in XY gonadal dysgenesis

In order to evaluate the role of SRY in the determination of the testis, we sequenced the conserved domain of the SRY gene in 8 patients with 46,XY gonadal dysgenesis and 3 patients with related disorders, and compared our data with those obtained in 6 other similar studies. In our study, a 609-bp fragment of SRY was amplified by the polymerase chain reaction and the internal conserved motif was sequenced. SRY sequences did not differ from those in normal males in any of our patients. Overall, 5 de novo mutations have been identified among 56 patients with sporadic XY gonadal dysgenesis (8.9%), and 2 de novo mutations have been identified among 18 patients with related conditions (11%). The unexpectedly low frequency of mutations within the SRY conserved domain in these patients could be caused by undetected Y-linked mutations outside the conserved domain in regions that control transcription during development (e.g., promotor/enhancer regions) or to downstream mutations in other sex-determining genes that need not map to the Y.

EFFICACY OF INTRAVENOUS GAMMAGLOBULIN IN THE TREATMENT OF PNEUMOCYSTIS CARINII PNEUMONIA IN THE RAT MODEL

The efficacy of commercially-prepared IV infusions of pooled human immunoglohulin G (IVIG) was evaluated in the treatment of Pneumocystis carinii pneumonia (PCP) in the immunosuppressed rat model to ascertain whether such treatment might prove feasible in the managment of pediatric subjects with PCP. Forty-eight rats were divided into six groups: (1) controls (C), (2) controls given IV human gammaglohulin infusions (C-I), (3) immunosuppressed rats given short-term cortisone (STC), (4) immunosuppressed rats given short-term cortisone and IV human gammaglobulin infusions (STC-I), (5) immunosuppressed rats given long-term cortisone (LTC), and (6) immunosupressed rats given long-term cortisone and IV human gammaglobulin infusions (LTC-I). An enzyme-linked immunosorbant assay (ELISA) was employed to monitor PC-specific endogenous and exogenously administered IgG throughout the test period and toluidine hlue ‘0’ stains were performed to determine the degree of P. carinii infection in rat lung. Lung infection analysis showed statistical equivalence in STC, STC-I, and LTC-I. However, LTC-I lungs contained significantly fewer (P<.05) cysts than did LTC rats not treated with IVIG. IVIG appeared efficacious in reducing the number of cysts in the lungs of immunosuppressed rats with long-term cortisone. This study suggests a significant role for humoral immune defenses in combating PCP and warrants controlled studies in the use of IVIG in the pediatric. patient with PCP.